Pharmacologic targeting of murine double minute 2 (MDM2) represents one of the most compelling strategies for therapeutic reactivation of wild-type p53 in hematologic malignancies. The MDM2-p53 autoregulatory loop is a central regulator of cellular stress responses, and in myeloid neoplasms-including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN)-p53 is frequently retained but functionally suppressed through MDM2 overexpression and oncogenic signaling, notably via JAK-STAT activation. Over the past decade, successive generations of MDM2 inhibitors have translated structural and mechanistic insights into clinical investigation, yielding critical lessons regarding dosing paradigms, hematologic toxicity, biomarker-driven patient selection, and mechanisms of resistance, including TP53-mutant clonal selection. While early phase III trials in AML were negative, recent studies in myelofibrosis demonstrate clinically meaningful spleen, symptom, and molecular responses, supporting disease-modifying potential in TP53-wild-type settings. Adaptive platform designs and rational combinations with JAK inhibitors, BCL-2 antagonists, and interferons have further refined therapeutic strategies. Emerging MDM2 degraders and next-generation agents aim to overcome feedback limitations and improve therapeutic index. This review integrates mechanistic foundations, clinical development, resistance biology, and future directions, highlighting how decades of basic science have reshaped p53 reactivation into a precision therapeutic paradigm in myeloid disease.

Spiritual and religious concerns are an integral yet often overlooked component of distress in cancer care. The National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) includes a "spiritual/religious concerns" item on its Problem List, but little is known about how this item is used or how it informs clinical care.

This targeted review examined how spiritual distress is identified and addressed using the DT in oncology settings. A PubMed search yielded 44 articles; six met inclusion criteria. Most studies were cross-sectional, conducted outside the United States, and varied widely in design, populations, and measurement tools.

Findings suggest that spiritual/religious concerns are endorsed by a meaningful subset of patients-especially during active treatment or at critical points such as diagnosis or recurrence-and often coincide with high distress scores. However, prevalence rates varied significantly (5%-60%), and few studies evaluated whether positive screens led to referrals or meaningful spiritual support. Only two studies used validated measures of spiritual well-being alongside the DT, and some findings-such as unexpectedly strong correlations between spiritual well-being and anxiety/depression-warrant further investigation.

Despite its inclusion in a widely used screening tool, the spiritual/religious concerns item remains underutilized and poorly understood. This review identifies major gaps in understanding when and how spiritual concerns arise, what influences their reporting, and how needs are addressed in practice. In the United States, where the DT is routinely collected, these gaps present a clear opportunity for targeted research and implementation efforts to improve holistic, values-aligned cancer care through better spiritual support integration.

Carbon-11 methionine positron emission tomography (¹¹C-methionine PET; Met-PET) is widely used in neuro-oncology for preoperative tumor characterization, differentiating recurrence from radiation necrosis, and determining stereotactic biopsy targets. Although its role in gliomas has been well established, evidence supporting its value in germ cell tumors, particularly teratomas, remains limited. An 18-year-old man presented with diplopia, photophobia, and a headache. Magnetic resonance imaging (MRI) revealed a pineal tumor. Serum AFP was 31.5 pg/mL, serum β-HCG < 1.0 mIU/mL, and CSF PLAP 23.6 pg/mL. After three courses of CARE chemotherapy and local radiotherapy, gross total resection was performed at another hospital. He subsequently developed hydrocephalus and underwent endoscopic third ventriculostomy at our institution. MRI and Met-PET showed no residual lesions. Additional ICE chemotherapy resulted in the normalization of tumor markers. However, MRI performed 4 months after resection demonstrated a new enhancing lesion in the right posterior thalamus, and Met-PET revealed new uptake (SUVmax, 2.64; TNR, 2.08), suggesting recurrence. A second craniotomy achieved gross total resection of the whitish, elastic, well-demarcated lesion. Histopathology showed mainly granulomas with inflammatory changes, but no viable tumor cells. The postoperative course was uneventful, and no recurrence has been observed for 3 years. This case suggests that in germ cell tumors, particularly teratomas, Met-PET findings may be misleading and do not necessarily indicate viable tumor tissue. Further studies are required to clarify the clinical significance of Met-PET for teratomas.

The advancement of single-cell RNA sequencing and spatial transcriptomics has enabled the inference of cellular interactions in a tissue microenvironment. Despite advances in cell-cell interaction inference, methods capable of mapping the influence of ligands on downstream target genes across spatial niches harboring specific cell type composition, crucial for resolving niche-specific relationship between ligands and their downstream targets are still lacking. Here, we present Renoir for charting the ligand-target activities across a spatial topology, delineating spatial communication niches harboring specific ligand-target activities and spatially mapping pathway-level activity of genesets. Across spatial datasets with varying resolution (spot to single-cell) ranging from development to disease, Renoir infers cellular niches with distinct ligand-target interactions, spatially maps pathway activities, and identifies context-specific cell-cell interactions, including hepatocyte-macrophage interactions in fetal liver and interactions between onco-fetal and bipotent cells in hepatocellular carcinoma. Renoir uncovers biological insights and therapeutically-relevant cellular crosstalk from spatial transcriptomics data.

Objective: To investigate the efficacy and safety of 36 000 IU recombinant human erythropoietin (rhEPO) in the treatment of cancer-related anemia (CRA) and to evaluate whether 36 000 IU rhEPO can serve as a rational "reduced-dose alternative" to the 40 000 IU rhEPO regimen. Methods: The multicenter, open-label, non-inferiority, randomized controlled trial was conducted from March 2023 to July 2024 across 12 hospitals in China, including Liaoning Cancer Hospital. A total of 119 patients with CRA were enrolled and randomly assigned to receive the 36 000 IU rhEPO (n=61) or 40 000 IU rhEPO (n=58). The primary efficacy endpoint was the change in hemoglobin (Hb) levels from baseline at weeks 9-13. Secondary efficacy endpoints included hematologic and other biochemical parameters, transfusion requirements, quality of life (QOL), which was assessed by QOL scores and Karnofsky performance status (KPS) scores, and overall survival. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). Results: The least-squares mean changes in Hb from baseline to weeks 9-13 were (12.9±2.3) g/L in the 36 000 IU group and (13.4±2.4) g/L in the 40 000 IU group. Analysis of covariance showed no statistically significant difference between groups (F=-0.21, P=0.836), with a between-group difference of (-0.5±2.5) g/L (95% CI: -5.4 g/L, 4.4 g/L). The lower limit of the 95% CI (-5.4 g/L) exceeded the predefined non-inferiority margin of -10 g/L, indicating non-inferiority of the 36 000 IU dose compared to the 40 000 IU. At week 13, the proportions of patients with Hb increase ≥10 g/L were 82.0% (50/61) in the 36 000 IU group and 86.2% (50/58) in the 40 000 IU group, with no significant difference between groups (Q_mh=0.40, P=0.527). The average weekly transfusion rate was 2.0% in both groups. No significantly significant differences were observed between the two groups in terms of changes in hematocrit, reticulocyte percentage, folate, vitamin B₁₂, albumin, iron metabolism markers, QOL scores, KPS scores, or overall survival (all P＞0.05). Regarding safety, the incidence of TEAE was 80.3% (49/61) in the 36 000 IU group and 84.5% (49/58) in the 40 000 IU group, with nausea, fever, and fatigue being the most common symptoms (incidence＞5%). No drug-related serious adverse events were reported, and there were no significant differences between the groups (P＞0.05). Conclusions: The 36 000 IU dose of rhEPO is non-inferior to the 40 000 IU dose in terms of efficacy and has a favorable safety profile for the treatment of CRA. These findings support the use of 36 000 IU rhEPO as a reasonable clinical option for managing CRA.

Osteosarcoma is the most common bone cancer in children and young adults. Its prognosis has not improved significantly since the introduction of the chemotherapy regimen established about 40 years ago, highlighting the need for new therapeutic strategies.

The present study was undertaken to assess the effectiveness of combined inhibition of two promising drug targets, ATR and ribonucleotide reductase (RNR), in osteosarcoma cells.

The ATR inhibitor berzosertib and the RNR inhibitors triapine and didox were tested in TP53 wild-type (U2OS, MG-63) and mutant (SaOS-2) osteosarcoma cell lines. Combination effects were examined by flow cytometric analysis of cell death, loss of the mitochondrial membrane potential and DNA fragmentation as well as by caspase 3/7 activity assay and real-time RT-PCR. The drug interactions were evaluated using combination index analysis. Single treatment with ATR or RNR inhibitors resulted in mild to moderate effects, whereas combined treatment resulted in strong and synergistic effects. ATR and RNR inhibitors cooperated to elicit loss of the mitochondrial membrane potential, to activate caspase 3/7 and to trigger DNA fragmentation, suggesting that the combination of ATR and RNR inhibitors induced an apoptotic form of cell death. The cytotoxic effects were independent of TP53 mutational status.

Our study demonstrates that combined inhibition of ATR and RNR was effective in osteosarcoma cells. These in vitro findings offer support for investigating in vivo the potential of a combination of ATR and RNR inhibitors as a new treatment strategy for osteosarcoma.

This systematic review aimed to identify robust clinicopathologic predictors of overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS) following radical cystectomy (RC) from published prediction models. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations were followed, and the study was registered in PROSPERO (CRD42024509410). MEDLINE (Ovid) and Embase (Elsevier) were searched from inception to January 2024 for studies developing or validating multivariable prediction models in patients undergoing RC for non-metastatic bladder cancer. Data were extracted following the CHARMS checklist, and risk of bias was assessed using the PROBAST (Prediction model Risk Of Bias Assessment) tool. Pooled hazard ratios (HRs) were estimated with DerSimonian-Laird random-effects models. Seventy-seven studies involving survival models met the inclusion criteria: 36 for OS, 44 for CSS, and 26 for RFS. For OS, adverse predictors included advanced age (HR 1.03, 95% confidence interval [CI] 1.02-1.04), gender (female) (HR 1.08, 95% CI 1.01-1.14), higher pathologic T stage, lymph node involvement (HR 1.91, 95% CI 1.70-2.14), lymphovascular invasion (LVI) (HR 1.49, 95% CI 1.40-1.58), positive surgical margins (HR 1.74, 95% CI 1.46-2.06), and concomitant carcinoma in situ (HR 1.09, 95% CI 1.03-1.16). Neoadjuvant (HR 0.66, 95% CI 0.47-0.93) and adjuvant chemotherapy (HR 0.74, 95% CI 0.71-0.76) and compliance with pentafecta criteria (HR 0.49, 95% CI 0.30-0.79) were associated with improved OS. CSS displayed similar prognostic patterns, with additional associations for lymph node density, hydronephrosis, sarcopenia, and elevated neutrophil-lymphocyte ratio. This meta-analysis identified consistent clinicopathologic predictors of adverse oncological outcomes after RC for bladder cancer. Systematic assessment of these variables allows more accurate postoperative prognostic stratification and supports clinical decision-making regarding adjuvant treatment selection, surveillance intensification, and patient counseling.

To improve the effectiveness and efficiency in radiation therapy, various treatment modalities and fractionation schemes have been introduced and combined for cancer treatment. Biological effective dose (BED) and equivalent dose in 2 Gy fraction (EQD₂) are used to evaluate and compare different modalities and fractionations and also used to determine dose prescriptions for new radiation schemes. BED and EQD₂ are functions of α/β and the accuracy of α/β value is essential. A single α/β value of 10 Gy has been used for cervical cancer in clinical practice. However, our previous study first found that cervical cancer has a broad range of α/β values across in vitro studies that follow a right-skewed log-normal distribution. If patient populations follow such a distribution, it may have potential impact on radiation therapy for cervical cancer.

To investigate the impact of variation in the α/β of cervical cancer on the expected EQD₂ associated with clinical outcome for cervix cancer patients treated with radiation therapy and how that variance could influence the determination of alternate fractionation schemes.

A right-skewed log-normal distribution of experimentally derived α/β values was applied to a reference tumor control probability (TCP) curve generated from cervical cancer patients treated with radiation, and a population of patients following that distribution were simulated using Monte Carlo sampling. An alternate equation for equivalent dose in 2 Gy fractions (EQD₂) was derived that considered variance in α/β and was used to generate new values and associated TCP curves that could be plotted on a common EQD₂ axis. Convolution curves of TCP and normal tissue complication probability (NTCP) were generated to determine the potential shift in optimal dose and probability of risk-free local control (RFLC). Theoretical treatment failure rates were generated to evaluate changes in rates of treatment outcomes.

Variation in α/β obtained from published experimental results produced potential losses in TCP of up to 24% in the range of clinical interest. RFLC curves predicted an optimal treatment dose of 95 Gy EQD₂ when applying our most probable α/β of 4.25 Gy, 10 Gy higher than that predicted by the reference curve. The α/β distribution saw a decrease in RFLC of 17%. To achieve a TCP of 90%, possible HDR fractionation schemes ranged from 56 Gy in 14 fractions to 32 Gy in 2 fractions, with the associated increase in normal tissue dose ranging from 11 to 16 Gy EQD₂.

The distribution of cervical cancer α/β values derived from experimental results produced significant changes in tumor control when applied to a reference TCP curve. TCP decreased with both the average and most probable α/β values. It is suggested that variance and heterogeneity in α/β be more explicitly incorporated to account for those patients that do deviate from the assumed constant value, especially in the case of evaluating different radiation schemes.

Hematopoietic stem cell transplantation (HSCT) is essential for curing high-risk or relapsed acute leukemia but entails lifelong morbidities. Adolescents and young adults may be particularly vulnerable; however, data on the global risk of long-term complications in survivors who underwent HSCT during adolescence are lacking. Using the French Leucémie Enfant Adolescent (LEA) cohort, we compared late complications and quality of life (QoL) in survivors transplanted at ≥15 years versus <15 years. We included 168 adolescents (≥15 years of age at HSCT) and 446 children (<15 years of age at HSCT) matched at best 1:3 on sex, type of leukemia, total body irradiation use, history of relapse, and follow-up duration. Cumulative morbidity was modelled with a five-state multistate model (0 to ≥4 complications). After a mean follow-up of 8.8 years for adolescents and 9.5 years for children, adolescents had a mean of 2.1±0.1 complications compared with 1.6±0.1 in younger survivors (p <0.001). Higher incidences were noted for cardiomyopathy, chronic kidney disease, secondary neoplasms, iron overload and osteonecrosis. The multi-state model revealed earlier onset and faster accumulation of complications in adolescents. QoL scores did not differ between groups. HSCT during adolescence is associated with earlier and heavier long-term morbidity, underscoring the need for age-tailored survivorship care and integration of AYA-specific risks into follow-up guidelines.

This study aimed to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemoimmunotherapy (CI) in unresectable esophageal squamous cell carcinoma (ESCC).

The study included patients with unresectable ESCC who received CCRT with or without induction CI at three cancer centers. Patients receiving concurrent immunotherapy were excluded. Propensity score matching (PSM) balanced baseline characteristics between groups.

A total of 519 patients were included. After PSM, 183 patients per group were selected. Induction CI significantly improved OS and PFS compared to CCRT alone, consistently. The median OS for CCRT and induction CI groups were 29.9 months (95% CI: 18.8-41.0) and not reached (HR: 0.57, 95% CI: 0.42-0.77, p < 0.001). The median PFS was 17.6 months (IQR: 13.7-21.4) versus 30.6 months (IQR: 17.3-43.8) (HR: 0.66, 95% CI: 0.51-0.86, p = 0.002). Responders to the induction CI had significantly better OS (HR: 0.22, 95%CI: 0.14-0.36, p < 0.001) than nonresponders. Subgroup analysis showed radiation dose escalation or consolidation immunotherapy did not further improve survival in the induction CI group.

The addition of induction chemoimmunotherapy to CCRT was associated with improved survival in patients with locally advanced unresectable ESCC, particularly in responders to induction chemoimmunotherapy, with acceptable toxicity. These findings warrant confirmation in prospective randomized trials.